title: Pharmacokinetics, distribution and excretion of PNA in rat by liquid chromatography mass spectrometry method.
abstract: The pharmacokinetic profiles, tissue distribution and excretion patterns of PNA in healthy male and female Sprague-Dawley rats following a single intra-duodenum administration were investigated by previously established LC-MS method. Absorption was rapid in rats as evidenced by a short time to maximum concentration (Cmax) of 0.050 ± 0.021, 0.072 ± 0.017 and 0.067 ± 0.018 h at the 25, 50 and 100 mg/kg dose level, respectively. The Cmax were 754.9 ± 196.1, 1187.8 ± 642.1 and 2082.1 ± 1,278.5 ng/mL and the AUC0-4 were 71.8 ± 25.9, 135.2 ± 69.9 and 303.3 ± 198.3 µg/L h, which showed linear with the intra-duodenum administration range from 25-100 mg/kg. Tissues were collected at 4 time points (3, 10 min, 1 and 3 h) after dosing at 50 mg/kg. Compare to the concentrations of plasma and other tissues, the level was particularly high in the liver and brain during 3 h. Bile/urine and feces samples were collected before dosing and till 24/48 h post-dosing. The mean cumulative excretion of unchanged PNA in bile amounted to 0.021% of the dose up to 24 h. The mean recoveries of unchanged PNA were 0.0095% and 0.043% of the dose up to 48 h in urine and feces, respectively. There was no significant difference in PNA concentration observed between male and female rats during the experiments.
authors.affiliation: Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing, P. R. China.
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.forename: Z-Z
authors.initials: ZZ
authors.lastname: Jiang
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: L-Y
authors.initials: LY
authors.lastname: Zhang
authors.forename: Z-J
authors.initials: ZJ
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D001087:Arabinonucleosides / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D006515:Hepatitis B virus / Q000187:drug effects*; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: C585590:2-amino-9-(2,3-dideoxy-2,3-dihydro-beta-D-arabinofuranosyl)-6-methoxy-9H-purine; D000998:Antiviral Agents; D001087:Arabinonucleosides